Some have suggested that pharmacokinetic factors play a role in cocaine- induced sensitization. We have previously found support for this position by demonstrating that only challenge doses of cocaine administered i.p., which do not circumvent "first-pass" metabolism are able to elicit sensitization. Intraventricular, intravenous, and intra- accumbens injections were ineffective. In the present series of studies we also found that cocaine pretreatment did not sensitize rats to intra- accumbens amphetamine or intra-ventricular CFTC, a potent cocaine analog. Intravenous injections of cocaine were, however, effective in producing "sensitization" following context-dependent cocaine administration. These findings further support the possibility that sensitization found in context-independent designs is heavily dependent on pharmacokinetic factors.